Recent experiments have used entubation of damaged nerves as a method for assessing the potential of nerve regenerative agents (Lundborg et al., Brain Res. 178: 573-576 (1979); Lundborg et al., J. Hand Surg. 5: 35-38, (1980)). In the models discussed in these references, the two ends of the damaged nerve are inserted and sutured into a pseudomesothelial-lined guide tube which is kept open by a stainless steel thread. Similar experiments (utilizing other materials for guide tubes) have demonstrated how the guide tube can substantially increase the distance over which damaged nerve tissue can be regenerated (Seckel, Muscle and Nerve 13: 785-800, (1990); Varon and Williams Peripheral Nerve Rep. Regen 1: 9-25, (1986); Williams et al. in Neurology and Neurobiology. The Current Status of Peripheral Nerve Regeneration, Gordon et al. eds.: 111-122 (1988); MacKinnon and Dellon, Surgery of the Peripheral Nerve: 561-572, (1988)). In the experiments described in these references, the regeneration of the nerve was shown to be enhanced by the presence of guide tubes, which resulted in an increase in the size of regenerating axons and a decrease in the time required for the regenerating nerve to bridge the damaged region.
The introduction of matrix-forming materials within the guide tube lumen has also been shown to have influences on nerve regeneration. Some of the substances which have shown some effect include collagen (Cordeiro et al. Plast. Reconstr. Surg., 88: 1013-1020), laminin (Madison et al. Exp. Neurol. 88: 767-772, (1985)) and fibrin clots (Williams et al. in Neurology and Neurobiology. The Current Status of Peripheral Nerve Regeneration, Gordon et al. eds.: 111-122 (1988); Williams and Varon, J. Comp. Neurol. 231: 209-220). In vitro experiments have also indicated that other matrix-forming materials, or materials attached to the guide tube surface, may enhance neuron outgrowth (Bailey et al. J. Neurocytol. 22: 176-184 (1993); Seckel, Muscle and Nerve 13: 785-800 (1990)).
The use of entubation repair for performing nerve grafts is also advantageous because the guide tube can be filled with materials containing growth factors which can potentially enhance nerve regeneration or improve certain characteristics of the regenerated axons. These improvements include increases in axon size and facilitation of myelin maturity, as well as increases in axon numbers. Some of the compounds which have shown some efficacy when applied to the peripheral nervous system either directly or systemically are listed in Table 1 of Seckel, Muscle and Nerve 13: 785-800, (1990). In particular, nerve-growth-stimulating agents which have been applied to injured nerves using a guide tube or nerve chamber include nerve growth factor (Rich et al. Exp. Neurol. 105: 162-170, (1989); Chen et al. Exp. Neurol. 103: 52-60, (1989)), fibroblast growth factor (Cordeiro et al. Plast. Reconstr. Surg. 83: 1013-1019, Seckel, Muscle and Nerve 13: 785-800, (1990)), insulin-like growth factor-1 (Nachemson et al., Growth Factors 3: 309-314, (1990); Sjoberg and Kanje, Brain Res. 485, 102-108, ACTH (Horowitz, Muscle & Nerve 120: 314-322, and a mixture of laminin, testosterone, GM-1 and catalase (Miller et al. Brain Res. 413: 320-326 (1987)). Growth factors and other agents have also been incorporated directly into guiding tubes made from resorbable or noresorbable polymers to allow a slow release of the growth factor over time (Aebischer et al., J. Neurosci. Res. 23: 282-289 (1989); Guenard et al. J. Neurosci. Res. 29: 396-400, (1991)).
Guiding filaments, usually consisting of threads of suture material, have also been used with limited success for the repair of damaged nerves (Alexander et al., Proc. Soc. Exp. Biol. Med. 68: 380-383, (1948); Stopford, Lancet, 1296-1297, (1920)). Despite these efforts, the use of guide materials to facilitate the growth of injured nerves has been largely abandoned in favor of nerve grafts. Experimentally, guiding filaments have been made of materials including laminin (Madison, et al., Exp. Neurol. 95: 378-390, (1987)), fibronectin (Knoops et al. Brain Res. Bull. 30: 433-437, (1993)), collagen (Valentini et al. Exp. Neurol. 98: 350-356, (1987)), carbon fibers (Khan et al., Brain Res 541: 139-145, (1991)) and coated filament materials (Yoshi et al. Exp. Neurol 96: 469-473). The use of these, and other materials, has been reviewed previously (Seckel, Muscle and Nerve 13: 785-800, (1990)).
While the use of entubation for the repair of damaged nerves has shown some promise, detracting factors, including possible inflammation or compression of the nerve, have led some experts in the field to conclude that the only damaged regions successfully bridged by entubation techniques were those which could be more appropriately closed using an end-to-end suture (Sunderland, Peripheral Nerve Injuries and Their Repair, p. 605 (1978)).